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Oncogenic Ras-mediated downregulation of Gadd153/CHOP is required for Ras-induced cellular transformation

Abstract

Oncogenic Ras proteins transform cells via multiple downstream signaling cascades that are important for cell proliferation and survival. Gadd153, also known as CHOP, is a growth inhibitory and proapoptotic protein and its expression is upregulated by many agents that induce apoptosis. Here, we report our novel findings that oncogenic Ras downregulates Gadd153 expression at both protein and mRNA levels and that such downregulation occurs, at least in part, via decreases in GADD153 mRNA stability. Gadd153 downregulation is specific to oncogenic Ras since another oncogenic family member R-Ras2/TC21 does not downregulate Gadd153. We further demonstrate that the expression of exogenous Gadd153 interferes with Ras-induced oncogenic transformation, which suggests that downregulation of Gadd153 appears to be an important mechanism by which oncogenic Ras promotes cellular transformation. Thus, oncogenic Ras-mediated cellular transformation also involves downmodulation of important molecules such as Gadd153 that negatively regulate cell growth and survival.

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Acknowledgements

This work was supported in part by the National Institutes of Health Grants DK62136-01, CA86945 and DK067271-01. Correspondence and requests for material should be addressed to YH.

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Correspondence to Ying Huang.

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Rong, R., Montalbano, J., Jin, W. et al. Oncogenic Ras-mediated downregulation of Gadd153/CHOP is required for Ras-induced cellular transformation. Oncogene 24, 4867–4872 (2005). https://doi.org/10.1038/sj.onc.1208660

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